Study reveals certain stomach acid suppressants hasten Alzheimer's in those with mild cognitive decline

A new study from researchers at Sunnybrook Research Institute has compared two classes of stomach acid suppressants, and found one in particular to be worse in terms of cognitive decline. The medications are among the most widely used drugs in the world.

The study was led by Mr. Che-Yuan (Joey) Wu, a graduate student in the laboratory of Dr. Walter Swardfager, a scientist in the Hurvitz Brain Sciences Program at Sunnybrook Research Institute (SRI) and assistant professor of Pharmacology & Toxicology at the University of Toronto.

Using a large U.S. national database and applying rigorous epidemiological methods, the team compared the effect of proton pump inhibitors (PPIs) versus histamine-2 receptor antagonists (H2RAs) on cognitive decline in 5,113 people. Study subjects were grouped according to cognitive status, either having normal cognition, mild-to-moderate Alzheimer’s disease, or mild cognitive impairment (MCI), a common precursor to Alzheimer’s disease.

“What spurred our interest in this is how common these medications are and therefore the potential magnitude of the problem,” says Dr. Swardfager. Among the results was a finding that could have a significant effect on how choices about these medications should be made. “Among people with mild cognitive impairment, H2RA use was associated with 40 percent faster progression to dementia than PPI use. H2RA use was also associated with faster memory decline over five years in people with mild-to-moderate Alzheimer’s disease.”

A hastening of cognitive decline was not seen in healthy older people who didn’t have Alzheimer’s disease or MCI.

Entitled “Gastric acid suppressants and cognitive decline in people with or without cognitive impairment,” the paper was recently published in Alzheimer's & Dementia: Translational Research & Clinical Interventions, a journal of the Alzheimer’s Association.

The findings are of public health importance, the authors note, because concerns have been raised in the medical literature over the years about a link between PPIs and dementia, and so some physicians might be tempted to switch their patients to H2RAs.

“By comparing PPIs and H2RAs head-to-head, we were able to answer an important clinical question – If a gastric acid suppressant is needed, which one might be more harmful?” says Mr. Wu, lead author of the paper. “Through the design of this study, that answer came out more clearly. Given the choice between the two for a patient with MCI or dementia, H2RAs were associated with faster cognitive decline than PPIs.”

The findings, adds Dr. Swardfager, may be of interest to not only physicians and pharmacists, but also to people looking for an over-the-counter (OC) medication for gastroesophageal reflux disease (GERD), either for themselves or for a family member. PPIs and H2RAs are available by prescription and OC.

“People are buying these like they’re buying ibuprofen, and they’re buying them for their elderly parents,” he says. “For most people, the decision probably doesn’t make that much difference. However, for people who are wrestling with MCI and potentially on their way to developing Alzheimer’s disease, which is a significant proportion of older people, that choice might actually make a difference in how they decline.”

H2RAs available in Canada include cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepsid). PPIs include omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet) and dexlansoprazole (Dexilant). The study compared users of these two classes broadly, but did not examine any of these drugs specifically, which will require larger studies.

Exactly how and why PPIs or H2RAs could hasten cognitive decline is an interesting avenue for future study, says Dr. Swardfager. He adds that it may be related to their anticholinergic effects, or how they block the activity of certain circuits in the brain which are already affected in early stages of Alzheimer’s disease.

Because this is an observational study, it is unlikely to immediately change practice, he adds. “I hope the answer to this specific question will get us closer to informing guidelines.”

Funding for the study was provided by the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), the Alzheimer’s Association (U.S.), Brain Canada, the Weston Brain Institute, Alzheimer’s Research U.K., the Michael J. Fox Foundation, and the Dr. Sandra Black Centre for Brain Resilience and Recovery. Data were provided by the National Alzheimer’s Disease Coordinating Centre, which is funded by the National Institute on Aging/National Institute of Health (U.S.).